JRA comprises a heterogenous group of childhood onset, chronic, autoimmune diseases with variable clinical presentations, outcomes and therapeutic responses. Little is available by way of laboratory testing to help the pediatric rheumatologists in the initial evaluation of patients although clinical evaluation has been a central and important method of establishing likely diagnoses and outcomes. The advent of the human genome project and its related technologies including those involving gene expression, i.e. gene chip analysis, provide extraordinary opportunities to add to this ability in a substantial and unique way. In the first specific aim, differential gene expression in peripheral blood and in joint fluids will be studied in order to comprehensively identify the gene transcripts which will form elements of profiles and which are likely to be involved in pathogenic pathways. Index genes, already shown to be relevant or likely to be so, will be used to identify genes with similar patterns of expression. It is likely this will lead to greater understanding of the mechanism of disease. This aim will include a cell specific analysis as well as the cross analysis between genomic data generated in other projects and gene expression data generated in this study. It is also likely, and supported by preliminary data, that these gene expression profiles can be determined in peripheral blood and in synovial fluids in a reproducible manner. The second aim then proposes to define gene expression profiles that correlate with onset type of JRA, particularly pauciarticular and polyarticular disease, and to determine the evolution of such profiles over a 2 year period. This will relate to clinical outcome as well as to changes with respect to drug therapies. The initial profiles in early disease will be part of a new onset data set (NODS) to be used by all four projects. In the third aim the ability of profiles present in the NODS to predict outcomes will be tested. The completion of this component will give profiles which will be of diagnostic, prognostic and therapeutic importance, which can be used in early disease.